Pathways regulating Na+/Ca2+ exchanger expression in the heart

Donald R. Menick, Lin Xu, Christiana Kappler, Wenjing Jiang, Patrick R. Withers, Neal Shepherd, Simon Conway, Joachim G. Müller

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

The Na+/Ca2+ exchanger (NCX1) is regulated at the transcriptional level in cardiac hypertrophy, ischemia, and failure. Following pressure overload, activation of MAPKs coincides with the kinetics of NCX1 gene upregulation in adult cardiocytes. Using adenoviral gene delivery, we begin to identify the molecular pathways responsible for upregulation of the exchanger gene. Inhibition of ERK with the MEK inhibitor UO126, the ERK protein phosphatase MKP-3, inhibited ERK activation, but only inhibited α-adrenergic-induced NCX1 upregulation by 30%. Overexpression of DN-JNK lowered basal NCX1 expression. Overexpression of activated MKK-3 was sufficient for α-adrenergic-stimulated upregulation of the reporter gene. Together, this data indicates that (1) JNK mediates basal cardiac expression of the NCX1 gene, (2) ERK and p38 play a role in α-adrenergic-stimulated NCX1 upregulation, and (3) p38 activation alone is sufficient for NCX1 upregulation.

Original languageEnglish (US)
Pages (from-to)237-247
Number of pages11
JournalAnnals of the New York Academy of Sciences
Volume976
StatePublished - 2002
Externally publishedYes

Fingerprint

Up-Regulation
Genes
Adrenergic Agents
Chemical activation
Phosphoprotein Phosphatases
Mitogen-Activated Protein Kinase Kinases
Calcineurin
Cardiomegaly
Reporter Genes
Pathway
Gene
Ischemia
Heart Failure
Kinetics
Gene Expression
Pressure
Activation

Keywords

  • Gene expression
  • Hypertrophy
  • Integrins
  • MAP kinases
  • Regulation
  • Signal transduction
  • Transgenic mice

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Menick, D. R., Xu, L., Kappler, C., Jiang, W., Withers, P. R., Shepherd, N., ... Müller, J. G. (2002). Pathways regulating Na+/Ca2+ exchanger expression in the heart. Annals of the New York Academy of Sciences, 976, 237-247.

Pathways regulating Na+/Ca2+ exchanger expression in the heart. / Menick, Donald R.; Xu, Lin; Kappler, Christiana; Jiang, Wenjing; Withers, Patrick R.; Shepherd, Neal; Conway, Simon; Müller, Joachim G.

In: Annals of the New York Academy of Sciences, Vol. 976, 2002, p. 237-247.

Research output: Contribution to journalArticle

Menick, DR, Xu, L, Kappler, C, Jiang, W, Withers, PR, Shepherd, N, Conway, S & Müller, JG 2002, 'Pathways regulating Na+/Ca2+ exchanger expression in the heart', Annals of the New York Academy of Sciences, vol. 976, pp. 237-247.
Menick DR, Xu L, Kappler C, Jiang W, Withers PR, Shepherd N et al. Pathways regulating Na+/Ca2+ exchanger expression in the heart. Annals of the New York Academy of Sciences. 2002;976:237-247.
Menick, Donald R. ; Xu, Lin ; Kappler, Christiana ; Jiang, Wenjing ; Withers, Patrick R. ; Shepherd, Neal ; Conway, Simon ; Müller, Joachim G. / Pathways regulating Na+/Ca2+ exchanger expression in the heart. In: Annals of the New York Academy of Sciences. 2002 ; Vol. 976. pp. 237-247.
@article{ee3456a798d04b6d86c785ac01c37826,
title = "Pathways regulating Na+/Ca2+ exchanger expression in the heart",
abstract = "The Na+/Ca2+ exchanger (NCX1) is regulated at the transcriptional level in cardiac hypertrophy, ischemia, and failure. Following pressure overload, activation of MAPKs coincides with the kinetics of NCX1 gene upregulation in adult cardiocytes. Using adenoviral gene delivery, we begin to identify the molecular pathways responsible for upregulation of the exchanger gene. Inhibition of ERK with the MEK inhibitor UO126, the ERK protein phosphatase MKP-3, inhibited ERK activation, but only inhibited α-adrenergic-induced NCX1 upregulation by 30{\%}. Overexpression of DN-JNK lowered basal NCX1 expression. Overexpression of activated MKK-3 was sufficient for α-adrenergic-stimulated upregulation of the reporter gene. Together, this data indicates that (1) JNK mediates basal cardiac expression of the NCX1 gene, (2) ERK and p38 play a role in α-adrenergic-stimulated NCX1 upregulation, and (3) p38 activation alone is sufficient for NCX1 upregulation.",
keywords = "Gene expression, Hypertrophy, Integrins, MAP kinases, Regulation, Signal transduction, Transgenic mice",
author = "Menick, {Donald R.} and Lin Xu and Christiana Kappler and Wenjing Jiang and Withers, {Patrick R.} and Neal Shepherd and Simon Conway and M{\"u}ller, {Joachim G.}",
year = "2002",
language = "English (US)",
volume = "976",
pages = "237--247",
journal = "Annals of the New York Academy of Sciences",
issn = "0077-8923",
publisher = "Wiley-Blackwell",

}

TY - JOUR

T1 - Pathways regulating Na+/Ca2+ exchanger expression in the heart

AU - Menick, Donald R.

AU - Xu, Lin

AU - Kappler, Christiana

AU - Jiang, Wenjing

AU - Withers, Patrick R.

AU - Shepherd, Neal

AU - Conway, Simon

AU - Müller, Joachim G.

PY - 2002

Y1 - 2002

N2 - The Na+/Ca2+ exchanger (NCX1) is regulated at the transcriptional level in cardiac hypertrophy, ischemia, and failure. Following pressure overload, activation of MAPKs coincides with the kinetics of NCX1 gene upregulation in adult cardiocytes. Using adenoviral gene delivery, we begin to identify the molecular pathways responsible for upregulation of the exchanger gene. Inhibition of ERK with the MEK inhibitor UO126, the ERK protein phosphatase MKP-3, inhibited ERK activation, but only inhibited α-adrenergic-induced NCX1 upregulation by 30%. Overexpression of DN-JNK lowered basal NCX1 expression. Overexpression of activated MKK-3 was sufficient for α-adrenergic-stimulated upregulation of the reporter gene. Together, this data indicates that (1) JNK mediates basal cardiac expression of the NCX1 gene, (2) ERK and p38 play a role in α-adrenergic-stimulated NCX1 upregulation, and (3) p38 activation alone is sufficient for NCX1 upregulation.

AB - The Na+/Ca2+ exchanger (NCX1) is regulated at the transcriptional level in cardiac hypertrophy, ischemia, and failure. Following pressure overload, activation of MAPKs coincides with the kinetics of NCX1 gene upregulation in adult cardiocytes. Using adenoviral gene delivery, we begin to identify the molecular pathways responsible for upregulation of the exchanger gene. Inhibition of ERK with the MEK inhibitor UO126, the ERK protein phosphatase MKP-3, inhibited ERK activation, but only inhibited α-adrenergic-induced NCX1 upregulation by 30%. Overexpression of DN-JNK lowered basal NCX1 expression. Overexpression of activated MKK-3 was sufficient for α-adrenergic-stimulated upregulation of the reporter gene. Together, this data indicates that (1) JNK mediates basal cardiac expression of the NCX1 gene, (2) ERK and p38 play a role in α-adrenergic-stimulated NCX1 upregulation, and (3) p38 activation alone is sufficient for NCX1 upregulation.

KW - Gene expression

KW - Hypertrophy

KW - Integrins

KW - MAP kinases

KW - Regulation

KW - Signal transduction

KW - Transgenic mice

UR - http://www.scopus.com/inward/record.url?scp=0036968797&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036968797&partnerID=8YFLogxK

M3 - Article

C2 - 12502566

AN - SCOPUS:0036968797

VL - 976

SP - 237

EP - 247

JO - Annals of the New York Academy of Sciences

JF - Annals of the New York Academy of Sciences

SN - 0077-8923

ER -